title: Enoyl coenzyme a hydratase domain-containing 2, a potential novel regulator of myocardial ischemia injury.
abstract: BACKGROUND
  We reported previously that Brown Norway (BN) rats are more resistant to myocardial ischemia/reperfusion (I/R) injury than are Dahl S (SS) rats. To identify the unique genes differentially expressed in the hearts of these rats, we used DNA microarray analysis and observed that enoyl coenzyme A hydratase-containing domain 2 (ECHDC2) is highly expressed (≈18-fold) in the SS hearts compared with the BN hearts.
  
  
  RESULTS
  RT-PCR, Western blot, and immunohistochemistry analyses verified that ECHDC2 was highly expressed in SS hearts compared with the BN hearts. ECHDC2 gene locates at chromosome 5 of rat and is expressed in mitochondria of the heart, mainly in cardiomyocytes but not in cardiofibroblasts. Overexpression of ECHDC2 in cells increased susceptibility to I/R injury while knockdown of ECHDC2 enhanced resistance to I/R injury. Furthermore, we observed that left anterior descending coronary artery ligation-induced myocardial infarction was more severe in the SS hearts than in the BN hearts or SSBN5 hearts, which was built on SS rats but had the substitution of chromosome 5 from BN rats. We also demonstrated that ECHDC2 did not alter mitochondrial O2 consumption, metabolic intermediates and ATP production. By gas chromatography-mass spectrometry, we found that ECHDC2 overexpression increased the levels of the cellular branched chain amino acids leucine and valine.
  
  
  CONCLUSIONS
  ECHDC2, a mitochondrial protein, may be involved in regulating cell death and myocardial injury. Its deficiency in BN rats contributes to their increased resistance to myocardial I/R compared with SS rats. ECHDC2 increases branched chain amino acid metabolism and appears to be a novel regulator linking cell metabolism with cardiovascular disease.
authors.affiliation: Department of Surgery, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Jianhai
authors.initials: J
authors.lastname: Du
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Li
authors.forename: Quan-Zhen
authors.initials: QZ
authors.lastname: Li
authors.forename: Tongju
authors.initials: T
authors.lastname: Guan
authors.forename: Qiuhui
authors.initials: Q
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Kirkwood A
authors.initials: KA
authors.lastname: Pritchard
authors.forename: Amadou K S
authors.initials: AK
authors.lastname: Camara
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004746:Enoyl-CoA Hydratase / Q000502:physiology*; D006836:Hydro-Lyases; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology*; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl
chemical_list: D006836:Hydro-Lyases; D004746:Enoyl-CoA Hydratase; C035867:methylglutaconyl-CoA hydratase
keywords: ECHDC2; branched amino acid metabolism; cell death; ischemia/reperfusion injury; myocardial infarction